The present invention is concerned with novel hydrogel contact lenses having excellent physical and optical properties and which can be worn in the eye with a minimum degree of discomfort or irritation and with the polymer compositions for preparing the lenses.
In the last few years, considerable attention has been directed to obtaining hydrogels of polymer compositions which are suitable for fabricating contact lenses.
For example, U.S. Pat. No. 3,532,679 to Steckler discloses hydrogel materials, which according to the patentee, form suitable contact lenses. Such hydrogels are obtained from certain relative amounts of a heterocyclic N-vinyl monomer containing a carbonyl functionality adjacent to the nitrogen in the heterocyclic ring such as N-vinyl-2-pyrrolidone, a vinyl ester or an acrylate ester, and a polyethylene glycol dimethacrylate cross-linking agent. According to Steckler, it is necessary to employ a polyethylene glycol dimethacrylate cross-linking agent in order to obtain hydrogels which have properties suitable for use as a contact lens. Moreover, Steckler indicates that much of the previous work with respect to hydrogels suitable for contact lenses was done employing either ethylene glycol dimethacrylate or polyethylene glycol dimethacrylate cross-linking agents. For instance, U.S. Pat. Nos. 2,976,576 and 3,220,960 to Otto Wichterle et al and an article by M. F. Refojo et al in the Journal of Applied Polymer Science, Volume 9, pages 2425-35 (1965) describe various hydrogel polymers including those employing an ethylene glycol dimethacrylate cross-linking agent for producing a hydrogel.
In addition, Seiderman in U.S. Pat. Nos. 3,639,524, 3,721,657, 3,767,731, and 3,792,028 suggests obtaining hydrogels from certain polymer compositions of N-vinyl-2-pyrrolidone wherein the suggested cross-linking agents are diesters of the type discussed by Steckler and Wichterle et al or are certain acids.
British Pat. No. 1,391,438 also suggests obtaining hydrogels from certain polymer compositions of N-vinyl-2-pyrrolidone wherein the cross-linking agent can be an alkylene glycol dimethacrylate (e.g., ethylene glycol dimethacrylate), divinyl benzene, diethylene glycol bis (allyl carbonate), or allyl methacrylate. Although divinyl benzene is suggested as a cross-linking agent in certain of the polymers, there is no explicit disclosure of using divinyl benzene in a contact lens. In fact, those compositions (Examples 7-10) suggested by the British patent for preparing contact lenses do not employ divinyl benzene. Moreover, those examples (Examples 1 and 2) which suggest divinyl benzene produced products which were "slightly distorted". Accordingly, such examples would not be suitable for preparing contact lenses because distortion cannot be tolerated in a contact lens. It is further noted that since the British Pat. No. 1,391,438 does not suggest any preference for divinyl benzene as a cross-linking agent, the use of such rather than an alkylene glycol dimethacrylate particularly when the polymer is obtained from a mixture which includes the corresponding alkylene glycol monoester is not clearly suggested. Such monoesters as obtained commercially contain a significant amount of diester. There is no incentive suggested in the British patent to employ the additional procedures, as applicants have, to remove as much of the diester from the monoester as is practical. Consistent with this is the fact that those compositions of the British patent which suggest an alkylene glycol monoester (Examples 11 and 12) employ the corresponding diester as a cross-linking agent.
O'Driscoll et al, for example, in U.S. Pat. No. 3,700,761 also suggest fabricating contact lens blanks from certain hydrogel compositions obtained from polyvinyl pyrrolidone, monoester of certain glycols such as hydroxyethyl methacrylate, and no more than about 0.2% by weight of a dimethacrylate. O'Driscoll et al emphasize that extreme importance of selecting the proper constituents and correct relative amounts of each for the fabrication of contact lenses. This criticality of constituents and their relative proportions for fabricating hydrogel contact lenses, which must possess a number of optical and physical characteristics, is discussed by Grucza in U.S. Pat. No. 3,807,398.
In addition to the necessary physical properties, hydrogel materials to be suitable for contact lenses must possess a number of important optical properties. For instance, the hydrogel must be transparent, colorless, and have a uniform refractive index. The material to be employed as a lens, when hydrated, should be capable of retaining the configuration of its optical surface for a relatively long period of time. Moreover, a lens obtained from a hydrogel material should be capable of retaining its optical characteristics when placed upon the eye. Furthermore, the desired shape should be retained without distortion, when going from the unhydrated state to the hydrated state. Also, the hydrogel material should be stable in the presence of light during its lifetime.
A lens material should also be permeable to tear fluid since drying of the outside surface of the lens may tend to cause fogging, which in turn impairs vision.
Therefore, an object of the present invention is to provide a polymer composition, useful for contact lenses, possessing the above-discussed combination of important properties.
It has been found according to the present invention that contact lenses can be obtained from hydrogels wherein the polymer is from a polymerizable mixture containing:
(1) polymerizable monoester of acrylic and/or methacrylic acid and polyhydric alcohol; PA1 (2) an alkyl acrylate and/or alkyl methacrylate and/or vinyl ester; PA1 (3) heterocyclic N-vinyl compound containing carbonyl functionality adjacent to nitrogen in the ring; and PA1 (4) as cross-linking agent, divinyl benzene and/or divinyl toluene. PA1 (A) a polymerized water-insoluble but water-swellable polymer composition from a polymerizable mixture consisting essentially of: PA1 wherein said polymerizable mixture contains from about 93.8 to about 51.8% by weight of (1); from about 1 to about 6% by weight of (2); from about 5 to about 40% by weight of (3); and from about 0.2 to about 2.2% by weight of (4) based upon the total weight of (1), (2), (3), and (4) in said polymerizable mixture; and PA1 (B) physiologically acceptable aqueous solution; wherein said hydrogel contains from about 30 to about 80% by weight of (A) based upon the total weight of (A) and (B), and from about 20 to about 70% by weight of (B) based upon the total weight of (A) and (B).
The ability to use divinyl benzene and/or divinyl toluene as a cross-linking agent for a hydrogel contact lens with the other polymerizable materials required by the present invention is quite surprising in view of the prior suggestions in the art concerning cross-linking agents for hydrogel contact lenses. For instance, even though Wichterle et al recognized that divinyl benzene was a cross-linking agent (i.e., see column 1, line 22, of U.S. Pat. No. 3,220,960), they did not suggest that divinyl benzene could be employed when preparing contact lenses. This failure to recognize divinyl benzene as being a suitable cross-linking agent in fabricating contact lens is especially evident by the disclosures of Shepherd and Gould. In particular, Shepherd and Gould, in U.S. Pat. No. 3,577,512, which is concerned with sustained release tablets and not contact lenses, suggest employing divinyl benzene or divinyl toluene, as well as the above-discussed diesters, in certain hydrogel polymeric compositions (e.g., see column 3, lines 12 and 13, and Example 21). On the other hand, Shepherd and Gould in U.S. Pat. No. 3,520,949 discuss contact lenses (column 3, line 14) but only suggest polyfunctional monomeric esters such as ethylene glycol dimethacrylate as the cross-linker (column 3, lines 24-27) and do not suggest divinyl benzene.
In U.S. Pat. No. 3,728,317, although Blank suggested divinyl benzene as a cross-linking agent in polymers vastly different from those of the present invention (e.g., polymers from methyl methacrylate and acrylic acid), the products produced were apparently somewhat hard (see Example 4). In fact, subsequently, Blank et al found that cross-linkers such as divinyl benzene yielded a hard product unsuitable for introduction into the eye (U.S. Pat. No. 3,927,206, column 1, line 61, to column 2, line 7).
However, contrary to the above-mentioned prior art indications, it has not only been found possible but desirable, to exclude diesters as cross-linking agent for fabricating hydrogel contact lenses and to use divinyl benzene and/or divinyl toluene along with the other materials required by the present invention. The use of divinyl benzene and/or divinyl toluene is advantageous since all commercially available hydroxyethyl methacrylate contains some amount of diester (ethylene glycol dimethacrylate), which at best is very difficult to measure. The removal of the diester, and the addition to the polymerization mixture of known quantity of divinyl benzene and/or divinyl toluene ensures a more reproducible polymerization from reaction batch to reaction batch. Another advantage to the use of divinyl benzene is that it is more efficient as a cross-linking agent in combination with the other materials in the polymerizable mixture than is, for example, ethylene glycol dimethacrylate. This in turn permits the addition of smaller amounts of divinyl benzene and/or divinyl toluene compared to diester, thus yielding lenses which are more hydrophilic yet still retain the property of high burst strength. Still another advantage to the use of divinyl benzene and/or divinyl toluene is that the final product has greater strength and is more resilient when compared to a product employing a diester such as ethylene glycol dimethacrylate as the cross-linker. This is believed at least in part to be due to the reduced distance between cross-linked chains.
It has also been observed that the hydrogel contact lenses of the present invention exhibit at most only a minimum amount of protein buildup when worn in the eye. Moreover, the hydrogel compositions of the present invention are quite flexible and elastic.
Also, results from preclinical studies with rabbits wearing lenses of the present invention showed no irritation or other ill effects. Moreover, no significant pathology has occurred in numerous cases of actual human wear during experimental clinical studies conducted over the last few years which confirms the safety of the lenses of the present invention.
Some other patents of interest which discuss contact lens materials are U.S. Pat. No. 3,621,079 to Leeds, U.S. Pat. No. 3,647,736 to Ewell, and U.S. Pat. No. 3,503,942 to Seiderman. Also, the criticality and difficulty in selecting the proper cross-linking agent in conjunction with other constituents is evidenced by U.S. Pat. Nos. 3,787,380, 3,758,448, and 3,772,235 to Stamberger.